Polychlorinated Biphenyls and Leukocyte Telomere Length: An Analysis of NHANES 1999–2002

Abstract

Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999–2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08–13.88) and 11.63% (95% CI: 6.18–17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose–response relationship (p-trend < 0.01). The association of the sum PCBs with longer LTL was found in both sexes.

Additionally, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin were associated with longer LTL. The age independent association between longer LTL and environmental exposures to PCBs, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin may support a role as tumor promoter of these compounds. Further studies to evaluate the effect of these compounds on LTL are needed to more fully understand the implications of our finding.

Highlights

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  NHANES 1999–2002 analysis of polychlorinated biphenyls (PCBs) and Dioxin-compounds and leukocyte telomere length (LTL)

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  Sum of PCBs were associated with longer LTLs evidence of a dose-response relationship.

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  Analyses stratified by sex confirmed the association of the sum PCBs with longer LTL in both sexes

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  Both dioxin-like and non-dioxin-like PCBs were associated with longer LTLs.

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  1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin were associated with longer LTL

Polychlorinated biphenyls are classified as probable carcinogens by the International Agency for Research on Cancer (IARC), with sufficient evidence in humans. Recently, the PCB126 congener was classified by IARC as a human carcinogen. This study conducted in a large nationally cross-sectional survey (n = 2431) report a strong and independent association between longer leukocyte telomere length and environmental exposures to PCBs, and dioxin-like compounds 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin. The associations between PCBs and some dioxin-like compounds reported in this study may support a role of these compounds as tumor promoters. However, further studies are needed to more fully understand the implications of the findings of this study.